In pursuit of our long-term goal of reducing breast cancer risk among women, Project 3 will expand on recent laboratory and epidemiologic fmdings which suggest that exposure to isoflavones during puberty may be the most critical period for breast cancer risk reduction. Early menarche is an established risk factor for breast and other estrogen-dependent cancers. Thus, to determine if isoflavone consumption is associated with the timing of menarche, we will conduct an observational study taking advantage of the naturally-occurring diversity of isoflavone intake in the San Francisco Bay Area. We propose to establish a cohort of 350 primarily Asian, largely Chinese, girls, age 10-13 at baseline, and follow them for two years to ascertain the onset of menarche. The study will take place in Cupertino, California and the surrounding area, which has an ethnically and culturally heterogeneous population, half of which is Chinese and includes a large number of immigrants as well as more westemly acculturated Chinese, providing substantial variation in dietary intake. Participating girls and their mothers will provide information on dietary history and a variety of lifestyle factors via in-person interviews. In addition, the girls will be asked to keep a 2-day food record and provide urine and blood (or buccal cell) samples. DNA samples will allow investigation of the independent and joint effects of genetic polymorphisms in estrogen synthesis and metabolism genes and their relationship to menarche. To our knowledge, this is the first study to address these issues. Analyses of these effects will take place in year 3 using the cross-sectional data from the baseline survey via logistic regression and in year 5 using the longitudinal data via Cox regression. Findings from the baseline analyses as well as some exploratory DNA sequencing analyses conducted in year 2 in conjunction with Core B will help direct analyses (or additional data collection) in the final years of the project. Finally, as part of this center grant we will establish a resource of plasma, DNA, urine, and epidemiologic data that will allow for future genetic, proteomic, and epidemiologic research spawned by the findings resulting from collaborations between Project 3 and the other Projects and Cores within this Center.